This project is concerned with exploring theoretical factors involved in mutagenesis and the initial steps in carcinogenesis. Recent experimental advances in the area of genetic engineering have provided new possibilities for studying the dependence of chemically induced mutational events on DNA sequence. We hope to use computer modeling to examine the physical chemical factors (charge distribution, chemical reactivity, and stereochemical and thermodynamic relationships) contributing to site specificity of chemical agents at the level of DNA damage. An additional area of interest is the effect of amino acid substitution on protein function.